JP2008195694A - Liver fat accumulation inhibitory agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a liver fat accumulation inhibitory agent derived from colored rice and useful for the prevention and treatment of lifestyle-related diseases such as hyperlipidemia, fatty liver, diabetes, etc., and a medicine and skin preparation for external use (cosmetic). <P>SOLUTION: This liver fat accumulation inhibitory agent comprises a pigment extract of the colored rice as effective components. The pigment extract is preferably a defatted rice bran extract of the colored rice. The liver fat accumulation inhibitory agent is characterized in that the colored rice is black rice or red rice. The beverages, foods, medicines and skin preparations for external use (cosmetics) comprise the above liver fat accumulation inhibitory agent. Further, as to the liver fat accumulation inhibition, in the fat metabolism passway shown in drawing, it is associated with (4) fat combustion acceleration, and not directly associated with effects caused by (1) fat absorption inhibition to (3) fat decomposition acceleration. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an inhibitor of liver fat accumulation derived from colored rice, and is applied as an active ingredient of, for example, pharmaceuticals, quasi drugs, foods and drinks, cosmetics (external preparations for skin) and the like.

  Excessive accumulation of neutral fat due to overeating or lack of exercise causes lifestyle-related diseases such as hyperlipidemia, fatty liver, and diabetes. Such lifestyle-related diseases are closely related to visceral fat type obesity (metabolic syndrome), and various materials for suppressing the accumulation of body fat have been recently studied.

Conventionally, as materials for suppressing the accumulation of body fat, chitosan, low-molecular sodium alginate, plant fiber derived from psyllium seed coat, Mizunara, Quercus tree seed seed powder (see Patent Document 1), heat-treated bittern (see Patent Document 2), for example , Black soybean extract (see Patent Document 3), tamarind seed coat extract (see Patent Document 4), and the like.
However, some of these materials are not sufficiently effective in suppressing the accumulation of triglycerides, and there is a demand for higher value-added materials in the market that are useful for the prevention and treatment of lifestyle-related diseases. It is.

JP-A-11-299451: Quercus tree seed seed powder Japanese Patent Application Laid-Open No. 2006-117658: Heated bitter gourd Japanese Patent Publication No. 2002-153240: Black soybean extract JP-A-9-291039: Tamarind seed coat extract Patent Publication No. 2004-91462: Carbohydrate absorption inhibitor derived from black rice Patent Publication No. 2004-143130: Suppression of blood sugar level increase from black rice Japanese Patent Application Laid-Open No. 2006-17654: Polyphenol glycoside derived from acerola (use example of external preparation for skin)

  As a main factor of fat accumulation, it is conceivable that fat is excessively stagnated in the fat metabolism pathway in the body (see FIG. 1). Therefore, when evaluating the effect of inhibiting accumulation of fat as a target, in the fat metabolism pathway, (1) suppression of fat absorption, (2) inhibition of fat accumulation, (3) promotion of lipolysis, (4) promotion of fat burning Often one of the effects is considered. In Patent Documents 1 to 4, fat accumulation is measured by measuring changes in the amount of triglycerol in blood and reduction in visceral fat (abdominal fat) related to (1) suppression of fat absorption to (3) promotion of lipolysis. The suppression effect is clarified.

  However, the suppression of hepatic fat accumulation is related to (4) promotion of fat burning in the fat metabolism pathway shown in FIG. 1, and (1) suppression of fat absorption to (3) action by promotion of lipolysis is directly involved. Not what you want. Therefore, in order to effectively prevent and treat lifestyle-related diseases, not only (1) suppression of fat absorption to (3) materials effective in promoting lipolysis but also (4) promotion of fat burning It is important to find materials that effectively suppress the accumulation of liver fat.

  Under such a background, the present inventors investigated the components and contents of extracts derived from various plants, and “black rice” and “red” containing abundant pigments such as anthocyanins and tannins. It came to pay attention to "rice". As a result of various experiments, these colored rice-derived pigment extracts contain a large amount of unknown compounds in addition to the pigment components described above, and these mixed products contain neutral fats in the liver. It has been found that the accumulation is effectively suppressed. In addition, it has been found that pigment extracts derived from colored rice have an action to improve hyperlipidemia due to an inhibitory action on liver fat accumulation, a preventive / therapeutic agent for metabolic syndrome, an inhibitory effect on weight gain, and an inhibitory action on increase in blood glucose level. Thus, the present invention has been completed.

It is an object of the present invention to provide a highly safe colored rice-derived liver fat accumulation inhibitor useful for the prevention and treatment of lifestyle-related diseases such as hyperlipidemia, fatty liver and diabetes.
In addition, another object of the present invention is to provide highly safe colored rice-derived foods and drinks, medicines and skin external preparations (cosmetics) that are useful for the prevention and treatment of lifestyle-related diseases such as hyperlipidemia, fatty liver, and diabetes. It is to provide.

The liver fat accumulation inhibitor of the present invention for solving the above-mentioned problems is characterized by containing a colored rice pigment extract as an active ingredient.
The liver fat accumulation inhibitor of the present invention is characterized in that the pigment extract is the defatted rice bran extract of colored rice.
The hepatic fat accumulation inhibitor of the present invention is characterized in that the colored rice is black rice.
The hepatic fat accumulation inhibitor of the present invention is characterized in that the colored rice is red rice.
The prophylactic / therapeutic agent for hyperlipidemia of the present invention is characterized by comprising the liver fat accumulation inhibitor.
The preventive / therapeutic agent for fatty liver according to the present invention is characterized by containing the above liver fat accumulation inhibitor.
The preventive / therapeutic agent for metabolic syndrome of the present invention is characterized by containing the above liver fat accumulation inhibitor.
The weight gain inhibitor of the present invention comprises the liver fat accumulation inhibitor (derived from red rice).
The suppression of an increase in blood glucose level according to the present invention is characterized by containing the liver fat accumulation inhibitor (derived from red rice).
The food / beverage products, medicines and skin external preparations (cosmetics) of the present invention are characterized by containing the liver fat accumulation inhibitor.

Accumulation of neutral fat in the liver occurs by increasing the amount of synthesis from free fatty acids or decreasing the amount of excretion as very low density lipoprotein (VLDL) from hepatocytes. Increased synthesis of triglycerides occurs as a result of the transmission of free fatty acids, an increase in available amounts (mobilized from diet and adipose tissue), a decrease in oxidation of free fatty acids in acetyl-CoA and liver, The decrease in the amount of exfoliated fat occurs by suppressing VLDL secretion by suppressing apolipoprotein, phospholipid and cholesterol.
According to the pigment-dye extract of colored rice according to the present invention, it is considered that the accumulation in the liver is suppressed by inhibiting or promoting necessary enzyme activity or the like in the process of lipid metabolism in the liver as described above. . And with the improvement of such liver function, the body's ability to metabolize lipids can be improved, and symptoms caused by excessive accumulation of neutral fat such as hyperlipidemia, fatty liver, diabetes and obesity can be improved. it can.
In addition, Patent Documents 5 and 6 are disclosed as conventional black rice-derived extracts related to fat metabolism, but there is no description or suggestion of the liver fat accumulation-inhibiting action as described above. .

  Metabolic syndrome is visceral obesity for a person and (1) hypertension, (2) hyperlipidemia or hypo-HDL cholesterol rollemia, (3) borderline diabetes or diabetes 3 According to the present invention, the improvement in the above (2) and (3) can be expected by improving the liver function. That is, the pigmented pigment extract of colored rice according to the present invention can be effectively used as a preventive / therapeutic agent for metabolic syndrome.

  In the present invention, the pigment extract of colored rice means a composition obtained by extracting pigment components from the epidermis and germ part of colored rice (ancient rice) such as black rice and red rice. According to the inventors' investigation, the pigment extract derived from black rice contains anthocyanin, proanthocyanin (condensed tannin) and the like, and the pigment extract derived from red rice contains tannin, proanthocyanin (condensed tannin). ) Etc. are included. The content of these known pigment components is about 20 to 30 wt% in the pigment extract, and the remaining components are unknown compounds whose structure is difficult to specify.

  Here, Patent Document 3 discloses that a pigment such as black soybean, that is, an anthocyanidin pigment (anthocyanin) and a derivative thereof have an excellent fat accumulation inhibitory action. According to this document, by extracting a pigment component from black soybean or the like, an anthocyanin compound having a purity of 90 wt% or more can be obtained, and this anthocyanin compound is used as an active ingredient for obesity prevention and obesity improvement / treatment. Has been shown to do.

  Patent Document 4 discloses that the tamarind seed coat extract contains a high concentration of proanthocyanin (proanthocyanidins). Proaproanthocyanidins having a polymerization degree of 2 to 80 have anti-obesity action, carbohydrates. It has been shown that there are activities of degrading digestive enzyme inhibitory action, blood sugar elevation inhibitory action, monosaccharide absorption inhibitory action, cholic acid adsorption and excretion action, cholesterol lowering action, blood triglyceride lowering action, and lipase inhibitory action.

However, the pigmented rice-derived pigment extract according to the present invention contains anthocyanin compounds and proanthocyanidins, but is a composite containing abundant other compounds in addition to these pigment components. The composition differs from the extract described in 4. Therefore, in the present invention, it is not necessary to purify the anthocyanin compound or proanthocyanidin when using the active ingredient.
In addition, the extraction components described in Patent Documents 3 and 4 are involved in (1) suppression of fat absorption to (3) promotion of lipolysis shown in FIG. It does not directly inhibit the accumulation of triglycerides by directly involved in the accumulation of fat. In this respect, the pigmented pigment extract of colored rice according to the present invention is different from the inventions described in Patent Documents 3 and 4 in the composition, action and effect of its constituent components.

  Embodiments of the present invention will be described below. In the following description, the form of using pigmented rice-derived pigment extract as an active ingredient of liver fat accumulation inhibitor will be described, but hyperlipidemia prevention / treatment agent, fatty liver prevention / treatment agent, metabolic syndrome prevention / The same usage pattern can also be adopted when a pigment extract derived from colored rice is contained in a therapeutic agent or a weight gain inhibitor that suppresses an increase in blood glucose level.

Ancient rice such as black rice or red rice can be used as the colored rice that is the raw material of the pigment extract.
Black rice is a kind of ancient rice native to Hanzhong Province, Shaanxi Province, China, and is also called purple black rice or purple rice. The surface of the brown rice is black and contains purple black pigment (anthocyanic pigment) in the pericarp, seed coat and germ. After 5 minutes (a little polished rice), the rice turns purple, and when all the rice cake is removed, it becomes a color close to white rice. There are two types of rice grains: japonica (short) and indica (long), and many of the latter are rice cakes. According to Kampo medicine, black rice has the effects of nourishing and enhancing energy, making the gastrointestines strong, supplementing and activating blood, strengthening lung function, restoring vision, and blackening hair It is considered. The pigment of black rice (anthocyanin) has been reported to have an antioxidant effect related to suppression of carcinogenesis by protecting the blood vessels, preventing arteriosclerosis, in addition to the effect of restoring eye strain.
As black rice varieties, Shikokuen, Kurodaen, Konan Kurome: Konan Kurome, Kuromasaki, Unnan Kuromome, Kohoku Murasaki Examples include black rice.

  Red rice is considered to be one of rice because most of the wild rice is red rice. The brown rice has a reddish brown color and contains red pigment (tannin) in the pericarp and seed coat. After 5 minutes (slightly polished rice), it turns pale red, and when all the rice cake is removed, it becomes white rice. There are two types of rice grains: jabonica (short) and indica (long), and in Japan, there are many jabonica varieties. Red rice varieties include Benikane, Benikichi, Benisuzaku, Benasuka, Taoyuan, Nakanoshima Red Rice (Naka) Noshima Akamai).

  In the present invention, as a raw material for obtaining a pigment extract, regardless of black rice and red rice varieties, only one of these varieties (including those listed above) may be used, Two or more kinds may be used in combination. The shape of the rice grain may be either Japonica (short grain) or Indica (long grain), or a mixture of these. As for the type of rice, either sticky rice or sticky rice may be used, or a mixture thereof may be used.

  Moreover, when extracting a pigment | dye component from colored rice, it is desirable to use defatted rice bran as a raw material. This is because the active ingredient is efficiently extracted from this defatted product by removing the oil in the rice bran. Furthermore, by using defatted rice bran, it becomes possible to produce a material with high added value from raw materials that are usually treated as waste.

  Preferred degreasing solvents include N-hexane, acetone and the like. In particular, when N-hexane is used as a degreasing solvent, the extracted oil can be used as an edible oil, and the pigment extract can be easily used as a food material.

As an extraction solvent for the pigment component, polar solvents such as water, methanol, ethanol, isopropyl alcohol, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, and ethyl acetate can be used. Two or more of these solvents may be mixed.
Desirably, when water or ethanol is used as the extraction solvent, the active ingredient is efficiently extracted. In particular, hydrous ethanol is an extraction solvent that is less likely to reduce the activity of the active ingredient during extraction and is preferable from the standpoint of safety in the use of the extract in food. The kind of water for extraction is not particularly limited, and tap water, distilled water, mineral water, alkaline ionized water, deep water and the like can be used.

  As the extraction temperature, for example, when water-containing ethanol is used, the extraction temperature is 20 to 80 ° C., preferably about 40 to 50 ° C. This is because if the extraction temperature is too low, it becomes difficult to extract the active ingredient, and if the extraction temperature is too high, the activity of the active ingredient tends to decrease.

  The water-containing ethanol as the extraction solvent has an ethanol concentration of 40 to 90% (wt / wt), desirably an ethanol concentration of 60 to 80% (wt / wt). The reason why the ethanol concentration is 40% (wt / wt) or more is that if the ethanol content is too small, the extraction amount of the active ingredient tends to be insufficient. The reason why the ethanol concentration is 90% (wt / wt) or less is that if the ethanol concentration is too high, the oil content in the rice bran is likely to dissolve in the water-containing ethanol. In addition, in order to improve the content rate of the active ingredient, the water-containing ethanol extraction may be repeatedly performed while changing the ethanol concentration stepwise.

  As a method for extracting the pigment extract, any method such as continuous extraction, immersion extraction, countercurrent extraction, and supercritical extraction can be adopted, and any apparatus can be used at room temperature or under reflux heating.

  Specifically, the raw material (defatted rice bran) is put into a treatment tank filled with the extraction solvent, and the active ingredient is eluted while stirring. For example, when water-containing ethanol is used as the extraction solvent, the extraction solvent is used in an amount of about 5 to 100 times (weight ratio) of the extraction raw material, and extraction is performed for about 30 minutes to 2 hours. The active ingredient is eluted in the solvent, and then filtered to remove the extraction residue to obtain an extract.

Thereafter, the extract is subjected to treatments such as dilution, concentration, drying and purification according to a conventional method to obtain a liver fat accumulation preparation according to the present invention.
As a method for purifying the pigment component, the pigment component is adsorbed through a synthetic adsorbent resin (Diaion HP-20 or the like), gel filtration resin or the like through the extract, and this is eluted with methanol, ethanol or the like, and concentrated under reduced pressure. For purification of red rice-derived pigment components, effective components can be efficiently recovered by using octadecyl silica gel (ODS).

  The liver fat accumulation inhibitor (pigment extract) of the present invention can be used as a material for various foods and drinks. Examples of food and drink include confectionery (gum, candy, caramel, chocolate, cookies, snacks, jelly, gummi, tablet confectionery, etc.), noodles (soba, udon, ramen, etc.), and dairy products (milk, ice cream, yogurt). ), Seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, tea, tea, carbonated drinks, sports drinks, etc.), health foods (tablets, capsules, etc.), nutrition Supplementary foods (such as energy drinks) are listed. These foods and drinks may be appropriately mixed with the liver fat accumulation inhibitor (pigment extract) of the present invention.

  These foods and drinks can be blended with various components depending on the type, for example, glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid. Acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, Food materials such as carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, pigments, fragrances and preservatives can be used.

  As a specific production method, a colored rice defatted rice bran pigment extract is spray-dried or freeze-dried together with powdered cellulose, and this is easily converted into powder, granules, tableting or solution to make food and drink (instant food, etc.) Can be contained. Moreover, the said pigment | dye extract is melt | dissolved, for example in fats and oils, ethanol, glycerin, or these mixtures, it can be made into a liquid state, and it can add to a drink or it can add to a solid food. If necessary, it can be mixed with a binder such as gum arabic or dextrin to form a powder or granules, which can be added to beverages or solid foods.

  As the addition amount when the liver fat accumulation inhibitor (pigment extract) of the present invention is applied to foods and drinks, since the main purpose is disease prevention and health maintenance, the total content of active ingredients in the foods and drinks It is preferably 1 to 20% by weight or less.

  The liver fat accumulation inhibitor (pigment extract) of the present invention may be used as a raw material for drugs (including pharmaceuticals and quasi drugs). It can be produced by appropriately blending the pigment extract of the present invention with a raw material for a pharmaceutical preparation. Examples of the pharmaceutical raw material that can be blended in the pigment extract of the present invention include excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, kaolin, crystalline cellulose, cocoa butter, hydrogenated vegetable oil, kaolin, talc, etc. ), Binder (distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrant (sodium alginate, agar, sodium bicarbonate) , Calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, starch, lactose, gum arabic powder, gelatin, ethanol, etc.), disintegration inhibitors (sucrose, stearin, cocoa butter, hydrogenated oil, etc.), absorption enhancers (quaternary) Ammonium base, sodium lauryl sulfate, etc.), Chakuzai (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (purified talc, stearates, polyethylene glycol, and the like) and the like.

  The administration method of the liver fat accumulation inhibitor (pigment extract) according to the present invention is generally administered orally in the form of tablets, pills, soft / hard capsules, fine granules, powders, granules, liquids, etc. It can be administered parenterally. When administered as a parenteral agent, it can be administered as a solution or with the addition of a dispersing agent, suspension, stabilizer, etc., by local tissue administration, intradermal, subcutaneous, intramuscular and intravenous injection, etc. it can. Moreover, it is good also as forms, such as a suppository.

The dosage may vary depending on the administration method, medical condition, age of the patient, etc., but for adults, it can be generally administered as 0.5 to 5000 mg as an active ingredient per day, and usually about 0.5 to 3000 mg for children.
The compounding ratio of the liver fat accumulation inhibitor (pigment extract) can be appropriately changed depending on the dosage form, but is usually about 0.3 to 15.0 wt% when administered orally or by mucosal absorption, In the case of parenteral administration, it should be about 0.01 to 10 wt%. In addition, since the dose varies depending on various conditions, a dose smaller than the above dose may be sufficient, or it may be necessary to administer beyond the range.

  The pigment extract of the present invention contains polyphenol components such as anthocyanins and proanthocyanins. According to Patent Document 7, the acerola-derived polyphenol glycosides are used to suppress the increase in blood glucose level (glucosidase inhibitory activity). It is disclosed that it is used as an external preparation, and the neutral fat accumulation inhibitor (pigment extract) of the present invention is also used as a skin external preparation (including cosmetics, pharmaceuticals, and quasi-drugs). Accumulation suppression can be expected.

Examples of cosmetics that can contain the liver fat accumulation inhibitor (pigment extract) of the present invention include, for example, emulsion, soap, facial cleanser, bath preparation, cream, emulsion, lotion, eau de cologne, shave cream, and shave. Lotion, cosmetic oil, suntan / sunscreen lotion, powder, foundation, perfume, pack, nail cream, enamel, enamel remover, eyebrow, blusher, eye cream, eye shadow, mascara, eyeliner, lipstick, lip balm, Shampoos, rinses, hair dyes, dispersions, cleaning agents and the like can be mentioned.
Examples of the form of a pharmaceutical or quasi-drug that can be blended with the pigment extract of the present invention include ointments, creams, and liquids for external use.

In addition to the pigment extract according to the present invention, the external preparation for skin of the above-described form includes ingredients, oils, and high-grade ingredients blended in external preparations for skin such as cosmetics and quasi-drugs as long as the effect of suppressing the accumulation of liver fat is not impaired. Alcohols, fatty acids, ultraviolet absorbers, powders, pigments, surfactants, polyhydric alcohols / sugars, polymers, physiologically active ingredients, solvents, antioxidants, fragrances, preservatives, and the like can be blended.
Examples are listed below, but the present invention is not limited to these examples.
(1) Examples of oil [ester-based oil phase components]: glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, Isocetyl isostearate, butyl stearate, butyl myristate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate , Diisopropyl adipate, isoaralkyl neopentanoate, glyceryl tri (capryl / caprate), trimethylolpropane tri-2-ethylhexanoate, trimethylotriisostearate Propane, tetra-2-ethylhexanoate pentaerythritol, cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isolaurate Stearyl, isotridecyl myristate, isocetyl myristate, isostearyl myristate, isocetyl palmitate, isostearyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl linoleate, octyldodecyl isoleate, isopropyl isostearate Cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethylene glycol dioctanoate Cole, ethylene glycol dioleate, propylene glycol dicaprate, propylene glycol di (capryl / capric acid), propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, triisopalmitine Glyceryl acid, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isononanoate, hexyl decyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerin oleic acid Ester, polyglycerol isostearate, dipropyl carbonate Dialkyl carbonate (C12-18), triisocetyl citrate, triisoaralkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyl decyl lactate, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate , Trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, Cholesteryl oleate, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, 12-stearoylhydroxystearin Isocetyl, 12-stearoyl-hydroxystearic acid stearyl 12-stearoyl-hydroxystearic acid isostearate, and the like.
[Hydrocarbon-based oil phase component]: Squalane, liquid paraffin, α-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, petrolatum and the like.
[Animal and vegetable oil and its hardened oil, and naturally derived wax]: beef tallow, hardened beef tallow, pork tallow, hardened tallow, horse oil, hardened horse oil, mink oil, orange luffy oil, fish oil, hardened fish oil, egg yolk oil, etc. Animal oil and its hardened oil, avocado oil, almond oil, olive oil, cacao butter, apricot oil, kukui nut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, safflower oil, shea butter, soybean oil, evening primrose oil, Perilla oil, tea seed oil, camellia oil, corn oil, rapeseed oil, hardened rapeseed oil, palm kernel oil, hardened palm kernel oil, palm oil, hardened palm oil, peanut oil, hardened peanut oil, castor oil, hardened castor oil, Vegetable oil such as sunflower oil, grape seed oil, jojoba oil, hardened jojoba oil, macadamia nut oil, medhome oil, cottonseed oil, hardened cottonseed oil, palm oil, hardened palm oil and the hardened oil thereof, beeswax High acid value beeswax, lanolin, reduced lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax and montan wax.
[Silicone-based oil phase component]: dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organopolysiloxane , Dimethylsiloxane / methylcetyloxysiloxane copolymer, dimethylsiloxane / methylstearoxysiloxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel , Acrylic silicone, trimethylsiloxysilicic acid, silicone RTV rubber and the like.
[Fluorine oil phase component]: Perfluoropolyether, fluorine-modified organopolysiloxane, fluorinated pitch, fluorocarbon, fluoroalcohol, fluoroalkyl / polyoxyalkylene co-modified organopolysiloxane, and the like.
(2) Examples of higher alcohols Lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol, octyldodecanol and the like can be mentioned.
(3) Examples of fatty acids Caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid , Erucic acid, 2-ethylhexanoic acid and the like.
(4) Examples of UV absorbers Paraaminobenzoic acid, amyl paraaminobenzoate, ethyldihydroxypropyl paraaminobenzoate, glyceryl paraaminobenzoate, ethyl paraaminobenzoate, octyl paraaminobenzoate, octyldimethyl paraaminobenzoate, ethylene glycol salicylate, salicylic acid Octyl, triethanolamine salicylate, phenyl salicylate, butylphenyl salicylate, benzyl salicylate, homomenthyl salicylate, benzyl cinnamate, octyl paramethoxycinnamate, 2-ethylhexyl paramethoxycinnamate, mono 2-diparamethoxycinnamate Glyceryl ethylhexanoate, isopropyl paramethoxycinnamate, diethanolamine salt of paramethoxyhydrocinnamic acid, diisopropyl diisopropylcinnamic acid Stealth mixture, urocanic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, dihydroxymethoxybenzophenone, dihydroxymethoxybenzophenone sodium disulfonate, dihydroxybenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone, tetrahydroxybenzophenone, Butylmethoxydibenzoylmethane, 2,4,6-trianilino-p- (carbo-2-ethylhexyl-1-oxy) -1,3,5-triazine, 2- (2-hydroxy-5-methylphenyl) benzotriazole , Methyl-O-aminobenzoate, 2-ethylhexyl-2-cyano-3,3-diphenyl acrylate, phenylbenzimidazole sulfate, 3- (4-methylbenzylidene) camphor, Isopropyl dibenzoylmethane, 4- (3,4-dimethoxyphenyl methylene) 2-ethylhexyl-2,5-dioxo-1-imidazolidin propionate,, and polymer derivatives and silane derivatives thereof.
(5) Examples of powders and pigments Red 104, Red 201, Yellow 4, Blue 1, Black 401 and other dyes, Yellow 4 AL lake, Yellow 203 BA lake and other lake dyes, nylon powder , Silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder, polyethylene powder, yellow iron oxide, red iron oxide, black Colored pigments such as iron oxide, chromium oxide, carbon black, ultramarine and bitumen, white pigments such as zinc oxide, titanium oxide and cerium oxide, extender pigments such as talc, mica, sericite, kaolin and barium sulfate plate, titanium mica Pearl pigments such as barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, metal salts such as magnesium silicate, Inorganic powders such as Rica and alumina, metal soaps such as aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, magnesium myristate, zinc laurate, zinc undecylenate, bentonite, smectite, boron nitride, etc. It is done. There are no particular restrictions on the shape of these powders (spherical, rod-like, needle-like, plate-like, irregular shape, flake-like, spindle-like, etc.) and particle diameter. These powders are conventionally known surface treatments such as fluorine compound treatment, silicone treatment, silicone resin treatment, pendant treatment, silane coupling agent treatment, titanium coupling agent treatment, oil agent treatment, N-acylated lysine treatment, The surface treatment may or may not be performed in advance by polyacrylic acid treatment, metal soap treatment, amino acid treatment, lecithin treatment, inorganic compound treatment, plasma treatment, mechanochemical treatment or the like.
(6) Examples of surfactant [anionic surfactant]: fatty acid soap, α-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, POE alkyl ether Sulfates, alkylamide sulfates, alkyl phosphates, POE alkyl phosphates, alkylamide phosphates, alkyloyl alkyl taurine salts, N-acyl amino acid salts, POE alkyl ether carboxylates, alkyl sulfosuccinates, alkyls Examples include sodium sulfoacetate, acylated hydrolyzed collagen peptide salt, and perfluoroalkyl phosphate.
[Cationic surfactant]: alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzaza chloride Examples thereof include luconium, amidopropyldimethylhydroxypropylammonium chloride behenate, diethylaminoethylamide stearate, dimethylaminopropylamide stearate, and lanolin derivative quaternary ammonium salts.
[Amphoteric surfactant]: Carboxybetaine type, amide betaine type, sulfobetaine type, hydroxysulfobetaine type, amide sulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, amidoamine type and the like.
[Nonionic surfactant]: Propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE sorbitol fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE Examples thereof include hydrogenated castor oil, POE castor oil, POE / POP copolymer, POE / POP alkyl ether, polyether-modified silicone lauric acid alkanolamide, alkylamine oxide, and hydrogenated soybean phospholipid.
[Natural surfactant]: Examples include lecithin, saponin, and sugar surfactant.
(7) Examples of polyhydric alcohols and sugars Ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol, 1,3 -Butylene glycol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylitol, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed isomerized sugar, sulfated trehalose, pullulan and the like. These chemically modified compounds can also be used.
(8) Examples of polymers Acrylic ester / methacrylic acid ester copolymer (plus size, manufactured by Kyoyo Chemical), vinyl acetate / crotonic acid copolymer (resin 28-1310, manufactured by NSC), vinyl acetate / croton Acid / vinyl neodecanate copolymer (28-2930, manufactured by NSC), methyl vinyl ether maleic acid half ester (Gantrez ES, manufactured by ISP), T-butyl acrylate / ethyl acrylate / methacrylic acid copolymer (rubymer) , BASF), vinyl pyrrolidone / vinyl acetate / vinyl propionate copolymer (Rubicol VAP, BASF), vinyl acetate / crotonic acid copolymer (Rubiset CA, BASF), vinyl acetate / croton Acid / vinyl pyrrolidone copolymer (Rubiset CAP, manufactured by BASF), vinyl pyrrolidone / acrylate copolymer (Rubiflex, BA SF), acrylate / acrylamide copolymer (Ultrahold, BASF), vinyl acetate / butyl maleate / isobornyl acrylate copolymer (Advantage, ISP), carboxy vinyl polymer (Carbopol, BF Goodrich), anionic polymer compounds such as acrylic acid / alkyl methacrylate copolymers (Pemulene, BF Goodrich) and acetic acid amphoteric compounds of dialkylaminoethyl methacrylate polymers (Yukaformer, Mitsubishi Chemical) Amphoteric polymer compounds such as octyl acrylate acrylate / hydroxypropyl acrylate / butyl aminoethyl methacrylate copolymer (AMPHOMER, NSC), quaternized vinylpyrrolidone / dimethylaminoethyl methacrylate (GAFQUAT, ISP) , Methyl vinyl imidazolium chloride Cationic polymer compounds such as vinyl / vinylpyrrolidone copolymer (rubicoat, manufactured by BASF), polyvinylpyrrolidone (rubiscol K, manufactured by BASF), vinylpyrrolidone / vinyl acetate copolymer (rubiscol VA, manufactured by BASF) ), Nonionic polymer compounds such as vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer 937, manufactured by ISP), vinylcaprolactam / vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer VC713, manufactured by ISP), etc. There is. Cellulose or derivatives thereof, keratin and collagen or derivatives thereof, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharide, xanthan gum, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabino Naturally derived polymer compounds such as galactan, gum karaya, gum tragacanth, alginic acid, albumin, casein, curdlan, gellan gum and dextran can also be suitably used.
(9) Examples of physiologically active ingredients Examples of physiologically active ingredients include substances that impart some physiological activity to the skin when applied to the skin. For example, whitening ingredients, anti-inflammatory agents, anti-aging agents, UV protection agents, slimming agents, tanning agents, antioxidants, hair growth agents, hair restorers, moisturizers, blood circulation promoters, antibacterial agents, bactericides, desiccants, A cooling sensation agent, a warming sensation agent, vitamins, an amino acid, a wound healing promoter, an irritation relaxation agent, an analgesic agent, a cell activator, an enzyme component, etc. are mentioned. Examples of these suitable ingredients include, for example, ashitaba extract, avocado extract, amateur extract, altea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, ginkgo biloba extract, fennel extract, turmeric extract, oolong tea extract, ages Extract, Echinacea leaf extract, Ogon extract, Oat extract, Oen extract, Barley extract, Hypericum extract, Oyster extract, Dutch mustard extract, Orange extract, Seawater dried product, Seaweed extract, Hydrolyzed elastin, Hydrolyzed wheat powder, Hydrolyzed silk , Chamomile extract, carrot extract, cormorant extract, licorice extract, calcade extract, oyster extract, kiwi extract, kina extract, cucumber extract, guanosine, gardenia extract, kumazasae Kiss, Clara extract, Walnut extract, Grapefruit extract, Clematis extract, Chlorella extract, Mulberry extract, Gentian extract, Black tea extract, Yeast extract, Burdock extract, Rice bran ferment extract, Rice germ oil, Comfrey extract, Collagen, Cowberry extract, Saisin extract , Psycho extract, Saitai extract, Salvia extract, Soybean extract, Sasa extract, Hawthorn extract, Salamander extract, Shiitake extract, Giant extract, Shikon extract, Perilla extract, Linden extract, Shimotake extract, Japanese peony extract, Ginger root extract, Birch extract, Japanese cedar Extract, Kizuta extract, Hawthorn extract, Elderberry extract, Achillea millefolium extract, Atlantic mint extract, Sage extract, Zeni mallow Extract, Senkyu Extract, Assembly Extract, Soybean Extract, Taiso Extract, Thyme Extract, Tea Extract, Fresh Coffee Bean Extract, Clove Extract, Chigaya Extract, Chimpi Extract, Toki Extract, Tokinsenka Extract, Tonin Extract, Spruce Extract, Dokudami Extract, Tomato Extract, Natto Extract, carrot extract, garlic extract, wild rose extract, hibiscus extract, buckwheat extract, parsley extract, honey, hamamelis extract, parietaria extract, toad extract, bisabolol, loquat extract, dandelion extract, burdock extract, butterfly extract, butcher bloom extract, Grape extract, propolis, loofah extract, safflower extract, peppermint extract, bodaiju extract, button extract, hop extract, matsue , Maronnier extract, Citrus extract, Mukuroji extract, Melissa extract, Peach extract, Cornflower extract, Eucalyptus extract, Yukinoshita extract, Yuzu extract, Yakuinin extract, Artemisia extract, Lavender extract, Apple extract, Lettuce extract, Lemon extract, Forsythia extract, Rose extract , Rosemary extract, roman chamomile extract, royal jelly extract and the like.
Biopolymers such as deoxyribonucleic acid, mucopolysaccharide, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, hydrolyzed eggshell membranes, amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidonecarboxylate , Moisturizing ingredients such as betaine, whey, trimethylglycine, oily ingredients such as sphingolipid, ceramide, phytosphingosine, cholesterol, cholesterol derivatives, phospholipids, ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, Anti-inflammatory agents such as hydrocortisone, vitamin A, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinamide, vitamin C ester, etc. Active ingredients such as vitamins, allantoin, diisopropylamine dichloroacetate, 4-aminomethylcyclohexanecarboxylic acid, antioxidants such as tocopherol, carotenoid, flavonoid, tannin, lignan, saponin, α-hydroxy acid, β-hydroxy acid, etc. Cell activators, blood circulation promoters such as γ-oryzanol and vitamin E derivatives, wound healing agents such as retinol and retinol derivatives, whitening such as arbutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, glutathione Agent, cephalanthin, licorice extract, red pepper tincture, hinokitiol, garlic iodide extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivative, calcium pantothenate, D-pan Tenenyl alcohol, acetyl pantothenyl ethyl ether, biotin, allantoin, isopropylmethylphenol, estradiol, ethinyl estradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor, salicylic acid, nonyl acid vanillylamide, nonanoic acid vanillylamide, pyroctonola Mines, glyceryl pentadecanoate, L-menthol, mononitroguaiacol, resorcin, γ-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormone, cantalis tincture, cyclosporine, zinc pyrithione, hydrocortisone, minoxidil, polymonostearate Examples include hair restorers such as oxyethylene sorbitan, mint oil, and Sasanishiki extract.
(10) Examples of antioxidants: sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolyl biguanide, nordihydroguaiaretic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxy Examples include plant extracts having an antioxidant effect such as toluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoid, flavonoid, tannin, lignan, saponin, apple extract and clove extract.
(11) Examples of solvents Purified water, ethanol, lower alcohol, ethers, LPG, fluorocarbon, N-methylpyrrolidone, fluoroalcohol, volatile linear silicone, next-generation chlorofluorocarbon and the like.

  Examples of the present invention will be described below. In addition, the Example shown below demonstrates in order to confirm various effect | actions, effects, etc. of the pigment | dye extract obtained by this invention, and the scope of the present invention is not limited to these products and production methods. Absent.

[Preparation of black rice pigment fraction (black rice pigment extract)]
For the black rice used as a raw material, the varieties “Shikokuen” was used.
Black rice bran (400 g) was degreased with 5 times the weight ratio of n-hexane, and then the rice bran was air-dried. Next, 50% ethanol was used for stirring extraction at room temperature. The extract was concentrated under reduced pressure at 40 ° C. or lower to obtain black rice extract (60 g). Black rice extract (20 g) was suspended in water and passed through a column filled with 20 times (400 g) of Diaion HP-20 in weight ratio. After washing with water (1 L), elution was successively performed with 50% methanol (1.5 L) and 100% methanol (1.5 L). These two eluates were combined and concentrated under reduced pressure at 40 ° C. or lower to obtain a black rice pigment fraction (11.5 g).

[Preparation of red rice pigment fraction (red rice pigment extract)]
For the red rice used as a raw material, the cultivar "Benaka" was used.
Red rice bran (400 g) was extracted at room temperature with 70% acetone in a 5-fold weight ratio. The same volume of water and n-hexane as the extract were added and shaken to distribute, and a water fraction was obtained. This water fraction was passed through an octadecyl silica gel (ODS) column to adsorb the contained components. The column was washed by passing water with 3 times the volume of ODS, and then eluted with 3 times the amount of ODS methanol. The eluate was concentrated under reduced pressure at 40 ° C. or lower to obtain a red rice pigment fraction (3.38 g).

[High-fat diet-fed mice]
Mice (ddY, male, 10 weeks old) were allowed to freely ingest a high fat diet (High Fat Diet 32, CLEA Japan) and tap water for 13 days. During this time, each sample suspended in water was orally administered once a day (200 mg / kg). The mice were fasted (22 h) from the day before the last day (day 12), and blood was collected from the abdominal aorta under ether anesthesia.
Serum was separated from the obtained blood after centrifugation, and triglycerides, cholesterol and blood glucose levels were measured using a commercially available kit (Wako Pure Chemical Industries). In addition, liver and visceral fat (cold testicular fat, perirenal fat) were removed and the wet weight was measured.

  On the other hand, a part of the liver (about 200 mg) was mixed with 19 times the amount of chloroform / methanol (2: 1) mixed solution, and homogenated under ice cooling. This was centrifuged (3000 rpm, 10 minutes), and the supernatant (200 mL) was collected in a test tube. After removing the solvent under a nitrogen stream, phosphate buffered physiological buffer (200 mL) was added to sufficiently disperse the residue. This suspension was measured for triglyceride and cholesterol concentrations using the kit described above. The results are shown in Table 1.

[Result]
As shown in Table 1, in terms of body weight, a tendency to suppress weight gain was observed in the red rice pigment fraction administration group. In the organ weight, the visceral fat was not changed, but the liver weight decreased in the red rice pigment fraction administration group.
On the other hand, in liver lipids, a significant decrease in triglycerides was observed in the black rice pigment fraction and red rice pigment fraction administration groups. Further, in these groups, serum triglycerides were also decreased, and in the red rice pigment fraction administration group, a tendency to decrease blood glucose level (glucose) was observed.

Based on the above results, black rice and red rice pigment fractions effectively prevent the accumulation of neutral fat (triglycerides) in the liver and suppress the accumulation of blood triglycerides, thereby preventing and treating metabolic syndrome. It turned out to be effective.
In addition, red rice pigment fraction has a stronger effect than black rice pigment fraction, and is effective in suppressing weight gain (obesity prevention and treatment) and normalizing blood glucose level (diabetes prevention and treatment). .

[Composition example]
The compounding example of the liver fat accumulation inhibitor (pigment extract) by this invention is shown. In the following formulation examples, a “pigment extract” is a pigment extract derived from black rice or red rice, preferably a pigment extract obtained from these defatted rice bran. According to each formulation example, it is possible to expect an improvement effect on hyperlipidemia, an improvement effect on fatty liver and an improvement effect on metabolic syndrome based on the liver fat accumulation suppression effect, especially when a pigment extract derived from red rice is added In addition to the above effects, it is also possible to expect an effect of improving diabetes and an effect of improving obesity.

As described above, according to the present invention, the following excellent effects can be obtained.
(a) By ingesting a safe extract derived from colored rice, it is possible to obtain an excellent liver fat accumulation inhibitory effect, and to prevent lifestyle diseases such as hyperlipidemia, fatty liver, diabetes, and lifestyle diseases. It can effectively prevent or treat the causing metabolic syndrome.
(b) Since it is a safe extract derived from colored rice, it can be used with peace of mind as a material for food and drinks and medicines.

It is a schematic diagram for demonstrating the fat accumulation inhibitory action in a fat metabolism path | route.

Claims (12)

  A liver fat accumulation inhibitor comprising a pigment extract of colored rice as an active ingredient.   The liver fat accumulation inhibitor according to claim 1, wherein the pigment extract is the defatted rice bran extract of the colored rice.   The liver fat accumulation inhibitor according to claim 1 or 2, wherein the colored rice is black rice.   The liver fat accumulation inhibitor according to claim 1 or 2, wherein the colored rice is red rice.   A hyperlipidemia preventive / therapeutic agent comprising the liver fat accumulation inhibitor according to any one of claims 1 to 4.   A fatty liver preventive / therapeutic agent comprising the liver fat accumulation-inhibiting agent according to any one of claims 1 to 4.   A preventive / therapeutic agent for metabolic syndrome, comprising the liver fat accumulation inhibitor according to any one of claims 1 to 4.   A weight gain inhibitor comprising the liver fat accumulation inhibitor according to claim 4.   The suppression of an increase in blood glucose level, comprising the liver fat accumulation inhibitor according to claim 4.   A food or drink comprising the liver fat accumulation-inhibiting agent according to any one of claims 1 to 4.   The chemical | medical agent containing the liver fat accumulation inhibitor as described in any one of Claims 1-4.   A skin external preparation comprising the liver fat accumulation inhibitor according to any one of claims 1 to 4.

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